Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of significant morbidity among hospitalized and community-dwelling persons. Initially described as a hospital- and healthcare-associated pathogen, new strains of community-associated MRSA (CA-MRSA) have emerged as an important cause of infection among of community-dwelling individuals. More recently CA-MRSA, as defined by pulsed-field gel electrophoresis, a form of DNA fingerprinting, has become a growing cause of healthcare-acquired infection. A large outbreak of infection caused by a highly pathogenic strain of CA-MRSA (USA300-0114) occurred at a large urban teaching hospital among post-partum women and newborns soon after discharge. Resistance to mupirocin was noted in a large proportion of isolates during the outbreak, which was an unusual and unexpected finding. Risk factors for colonization and infection with hospital-associated strains of MRSA (HA-MRSA) are fairly well established, but the risk factors for CA-MRSA colonization and infection in this high risk population remain poorly defined. By the use of novel, advanced statistical modeling, the current study aims to delineate the risk factors for colonization and infection with mupirocin-resistant and mupirocin-susceptible strains of CA-MRSA USA300-0114 during this outbreak. Given the dynamic nature of the newborn nursery, the setting in which transmission is suspected to have occurred, transmission dynamics and transmission rates will be determined using an open Susceptible-Infected-Recovered model. Finally, laboratory studies to determine the genetic makeup and other characteristics of the colonizing and infecting MRSA isolates will be performed in parallel with the clinical epidemiological investigations with the aim of determining mechanisms by which resistance to topical antimicrobial agents is spread and possible linkage between pathogen virulence and resistance. The proposed study will examine risk factors for colonization and infection in this population, however, some of the findings will likely be generalizable to CA-MRSA transmission in other populations both in the outbreak and non-outbreak setting. Furthermore, important information regarding development of resistance and mechanisms of resistance to topical agents commonly used in decolonization will be obtained. This information will ultimately have implications for the use of these agents in routine infection control and decolonization.